title: Uropathogenic Escherichia coli P and Type 1 fimbriae act in synergy in a living host to facilitate renal colonization leading to nephron obstruction.
abstract: The progression of a natural bacterial infection is a dynamic process influenced by the physiological characteristics of the target organ. Recent developments in live animal imaging allow for the study of the dynamic microbe-host interplay in real-time as the infection progresses within an organ of a live host. Here we used multiphoton microscopy-based live animal imaging, combined with advanced surgical procedures, to investigate the role of uropathogenic Escherichia coli (UPEC) attachment organelles P and Type 1 fimbriae in renal bacterial infection. A GFP+ expressing variant of UPEC strain CFT073 and genetically well-defined isogenic mutants were microinfused into rat glomerulus or proximal tubules. Within 2 h bacteria colonized along the flat squamous epithelium of the Bowman's capsule despite being exposed to the primary filtrate. When facing the challenge of the filtrate flow in the proximal tubule, the P and Type 1 fimbriae appeared to act in synergy to promote colonization. P fimbriae enhanced early colonization of the tubular epithelium, while Type 1 fimbriae mediated colonization of the center of the tubule via a mechanism believed to involve inter-bacterial binding and biofilm formation. The heterogeneous bacterial community within the tubule subsequently affected renal filtration leading to total obstruction of the nephron within 8 h. Our results reveal the importance of physiological factors such as filtration in determining bacterial colonization patterns, and demonstrate that the spatial resolution of an infectious niche can be as small as the center, or periphery, of a tubule lumen. Furthermore, our data show how secondary physiological injuries such as obstruction contribute to the full pathophysiology of pyelonephritis.
authors.affiliation: Department of Neuroscience, Swedish Medical Nanoscience Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Keira
authors.initials: K
authors.lastname: Melican
authors.forename: Ruben M
authors.initials: RM
authors.lastname: Sandoval
authors.forename: Abdul
authors.initials: A
authors.lastname: Kader
authors.forename: Lina
authors.initials: L
authors.lastname: Josefsson
authors.forename: George A
authors.initials: GA
authors.lastname: Tanner
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Molitoris
authors.forename: Agneta
authors.initials: A
authors.lastname: Richter-Dahlfors
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion; D004927:Escherichia coli Infections / Q000382:microbiology*; D005260:Female; D036781:Fimbriae Proteins / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000502:physiology*; D007668:Kidney / Q000382:microbiology / Q000503:physiopathology*; D009399:Nephrons / Q000382:microbiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000473:pathology*; D056689:Uropathogenic Escherichia coli / Q000502:physiology*
chemical_list: D036781:Fimbriae Proteins